The main objectives of this Phase II study are to evaluate the safety and efficacy of 5 day oral 5-FU given in combination with 776C85 with or without Leukocorin in the treatment of previously untreated or refractory metastatic colorectal cancer. The protocol will obtain preliminary data on whether the type of 5-FU resistance affects the antitumor activity of 5-FU plus 776C85. Quality of life (QOL) and validation of a site specific QOL module used as a supplement to a core questionairre will also be evaluated.